Department of Internal Medicine, Section of Infectious Diseases and Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Department of Medical Microbiology, Radboud University Center, Nijmegen, The Netherlands.
Clin Infect Dis. 2023 Jul 5;77(1):38-45. doi: 10.1093/cid/ciad141.
Invasive aspergillosis (IA) by a triazole-resistant Aspergillus fumigatus is associated with high mortality. Real-time resistance detection will result in earlier initiation of appropriate therapy.
In a prospective study, we evaluated the clinical value of the AsperGenius polymerase chain reaction (PCR) assay in hematology patients from 12 centers. This PCR assay detects the most frequent cyp51A mutations in A. fumigatus conferring azole resistance. Patients were included when a computed tomography scan showed a pulmonary infiltrate and bronchoalveolar fluid (BALf) sampling was performed. The primary end point was antifungal treatment failure in patients with azole-resistant IA.
Of 323 patients enrolled, complete mycological and radiological information was available for 276 (94%), and probable IA was diagnosed in 99/276 (36%). Sufficient BALf for PCR testing was available for 293/323 (91%). Aspergillus DNA was detected in 116/293 (40%) and A. fumigatus DNA in 89/293 (30%). The resistance PCR was conclusive in 58/89 (65%) and resistance detected in 8/58 (14%). Two had a mixed azole-susceptible/azole-resistant infection. In the 6 remaining patients, treatment failure was observed in 1. Galactomannan positivity was associated with mortality (P = .004) while an isolated positive Aspergillus PCR was not (P = .83).
Real-time PCR-based resistance testing may help to limit the clinical impact of triazole resistance. In contrast, the clinical impact of an isolated positive Aspergillus PCR on BALf seems limited. The interpretation of the EORTC/MSGERC PCR criterion for BALf may need further specification (eg, minimum cycle threshold value and/or PCR positive on >1 BALf sample).
烟曲霉所致三唑类耐药侵袭性曲霉病（IA）与高死亡率相关。实时耐药检测可更早启动适当的治疗。
在一项前瞻性研究中，我们评估了 AsperGenius 聚合酶链反应（PCR）检测在 12 个中心的血液病患者中的临床价值。该 PCR 检测可检测烟曲霉中最常见的赋予唑类耐药性的 cyp51A 突变。当 CT 扫描显示肺部浸润且进行支气管肺泡灌洗液（BALf）采样时，患者可纳入研究。主要终点是唑类耐药性 IA 患者的抗真菌治疗失败。
323 例患者中，276 例（94%）有完整的微生物学和影像学信息，276 例中诊断为可能的侵袭性曲霉病 99 例（36%）。293 例（91%）有足够的 BALf 进行 PCR 检测。116 例（40%）293 例中检测到曲霉 DNA，89 例（30%）中检测到烟曲霉 DNA。58 例（65%）耐药 PCR 检测结果明确，其中 8 例（14%）检测到耐药性。其中 2 例为唑类敏感性/唑类耐药性混合感染。其余 6 例患者中，1 例治疗失败。BALf 中半乳甘露聚糖阳性与死亡率相关（P=0.004），而单独的阳性曲霉 PCR 无相关性（P=0.83）。
基于实时 PCR 的耐药检测有助于限制三唑类耐药的临床影响。相比之下，BALf 中单独的阳性曲霉 PCR 的临床影响似乎有限。EORTC/MSGERC PCR 标准对 BALf 的解释可能需要进一步明确（例如，最小循环阈值和/或 1 个以上 BALf 样本阳性的 PCR）。
